Selective removal of low density lipoprotein (LDL) by dextran sulfate affinity adsorption was evaluated in patients with familial hypercholesterolemia (FH). Patients with both homozygous and heterozygous disease were eligible for treatment if their plasma LDL-cholesterol concentrations exceeded 180 mg/dl despite maximal drug and dietary management. The prototype dextran sulfate apheresis system (Liposorber LA- 15, Kanegafuchi, Japan) removed LDL without affecting HDL cholesterol or albumin concentrations, thus allowing return of autologous LDL-depleted plasma and avoiding the need for albumin-containing replacement solutions. One and one-half plasma volumes were processed every two weeks. Two homozygous and one heterozygous patient have completed the study. In these three individuals, the procedures effected a 70% reduction in total cholesterol and an 80% reduction in LDL cholesterol levels. Mean pre- procedure LDL-cholesterol levels were 228 plus/minus 29 mg/dl and post- procedure values were 48 plus/minus 5 mg/dl (n = 84). Lp(a) levels declined by 80% (72 plus/minus 32 to 14 plus/minus 4 mg/dl). Time-averaged HDL-cholesterol levels increased by 10% during the course of the aphereses. Serum albumin concentrations were not significantly affected by the procedures. The treatments were very well tolerated and no significant adverse reactions occurred. Our data suggest that dextran sulfate adsorption is a safe and effective way to selectively clear plasma of LDL-cholesterol, and has advantages, when compared to simple plasma exchange, of eliminating the need for colloid replacement solutions and promoting a more beneficial LDL/HDL cholesterol ratio. (The IDE number for the investigational device used in this study is G880069; the IDE holder is Kaneka America.)